Disease relevance of RTL1

• Here we analyzed the responses to synthetic peptides of HLA-A2.1-restricted CTL clones specific for melanoma antigens MART-1 and NA17-A [1].
• Partial protection against a challenge with NFSA(MART1) could be achieved with i.m. injections of a MART-1 expression plasmid or with systemic administration of an adenovirus vector expressing MART-1 [2].
• Tumor lesions in lymphoid and nonlymphoid tissues (metastatic lymph nodes and soft tissue/visceral metastases, respectively) were collected from stage III/IV melanoma patients and investigated for the presence and function of CD8 T cells specific for the tumor differentiation antigen Melan-A/MART-1 [3].
• A poorly immunogenic murine fibrosarcoma line (NFSA) was stably transfected with the MART-1 gene [2].
• We have investigated the possible usefulness of recombinant canarypox virus (ALVAC) encoding the melanoma-associated Ag, Melan-A/MART-1 (MART-1), in cancer immunotherapy, using a dendritic cell (DC)-based approach [4].

High impact information on RTL1

• Here we show that the imprinted mouse distal chromosome 12 locus encodes two miRNA genes expressed from the maternally inherited chromosome and antisense to a retrotransposon-like gene (Rtl1) expressed only from the paternal allele [5].
• Using fluorescent HLA-A*0201 tetramers containing the immunodominant Melan-A/MART-1 (Melan-A) tumor-associated antigen (Ag), we previously observed that metastatic lymph nodes of melanoma patients contain high numbers of Ag-experienced Melan-A-specific cytolytic T lymphocytes (CTLs) [6].
• High frequencies of naive Melan-A/MART-1-specific CD8(+) T cells in a large proportion of human histocompatibility leukocyte antigen (HLA)-A2 individuals [6].
• Analysis of a melanocyte-specific phenotype marker (MART-1) and a neuronal marker (Tuj1) revealed a subpopulation of melanoma cells that invade the chick periphery and express MART-1 and Tuj1 [7].
• The MCS1a sequence was found to comprise a portion of the long terminal repeats of a retrotransposon-like repeated element, termed CentA [8].

Chemical compound and disease context of RTL1

• We analyzed non-HLA-A*0201 peptide response profiles using HLA-A*0201-restricted epitopes from melanoma Ags MART-1/Melan A and glycoprotein 100 [9].
• Vitamin A activity of buriti (Mauritia vinifera Mart) and its effectiveness in the treatment and prevention of xerophthalmia [10].
• Melan A/MART-1 immunoreactivity in formalin-fixed paraffin-embedded primary and metastatic melanoma: frequency and distribution [11].

Biological context of RTL1

• Two of the autosomal gene members, Peg10 and Rtl1, are known to be imprinted, being expressed from the paternally inherited chromosome homologue [12].
• Furthermore, the methylation status of Rtl1 was assayed throughout development and was found to resemble that of actively, silenced repetitive elements rather than imprinted sequences [12].
• The cloning and expression of functional TCR genes which are capable of specifically recognizing MART-1 antigen provides reagents which could be used for the study of the mechanisms of T-cell/tumor antigen interactions and creates immortalized reagents which can facilitate studies requiring detection of the MART-1 antigen [13].
• One consistent feature of infection by ALVAC is that these viruses induce apoptosis, and we show cross-presentation of Ag when uninfected DC are cocultured with ALVAC MART-1-infected DC [4].
• Significantly, this Ag silencing is reversible, as removal of factor-containing supernatants from Melan-A/MART-1-expressing cells results in up-regulation of the promoter for the gene encoding this Ag, and renewed expression of the protein [14].

Anatomical context of RTL1

• Recognition of HLA-A2+ melanoma cell lines by the Jurkat clone 5 TCR+ cells, however, did not occur without the addition of exogenous MART-1 peptide [13].
• Generation of CD8+ and CD4+ T-cell response to dendritic cells genetically engineered to express the MART-1/Melan-A gene [15].
• Among the immunomodulators, the T-cell antigen MART-1 and the protease inhibitor alpha2-macroglobulin were detected in the melanocyte cell line but not in the tumor cells [16].
• T-cell receptor repertoire in matched MART-1 peptide-stimulated peripheral blood lymphocytes and tumor-infiltrating lymphocytes [17].
• Unexpectedly, however, whereas primed Melan-A/MART-1-specific CD8 T cells that circulate in the blood display robust inflammatory and cytotoxic functions, those that reside in tumor lesions (particularly in metastatic lymph nodes) are functionally tolerant [3].

Associations of RTL1 with chemical compounds

• Intron 9 carries a retrotransposon-like element, Tms1, which might be responsible for downstream deletion events in which a heptanucleotide, ATTAGCT, might have been involved [18].
• Heart-of-palm (Euterpe edulis Mart.) is a wild palm with a wide distribution throughout the Atlantic Rainforest [19].
• In this study we demonstrate transgene expression, including expression of the MART-1 gene, in DC transfected with plasmid DNA and cationic liposome complexes [20].
• Grossamide, and N-TRANS-caffeoyltyramine, were isolated for the first time from the seeds of ANNONA CRASSIFLORA Mart, and in the Annonaceae family [21].
• Modification of the parental immunodominant Melan-A/MART-1 peptide (MART-1(26-35)) by replacing the alanine with leucine (A27L) enhances its immunogenicity [22].

Other interactions of RTL1

• An extremely high genomic diversity was observed among the 879 strains typed by Southern blotting with a retrotransposon-like element from A. fumigatus (C. Neuvéglise, J. Sarfati, J. P. Latgé, and S. Paris, Nucleic Acids Res. 24:1428-1434, 1996) [23].
• Screening of genomic cosmid and plasmid clones derived from intron 3 of the HMGI-C gene for the presence of these RTVL-H sequences showed a cluster of these retrotransposon-like sequences in this region of HMGI-C [24].

Analytical, diagnostic and therapeutic context of RTL1

• A superagonist variant of peptide MART1/Melan A27-35 elicits anti-melanoma CD8+ T cells with enhanced functional characteristics: implication for more effective immunotherapy [25].
• Here, we show that autologous DCs from both HLA-A2-positive melanoma patients and normal healthy individuals that are transduced with an adenoviral vector containing the MART-1 antigen are capable of inducing both MART-1-specific CD8+ and CD4+ T cells in in vitro coculture [15].
• Replication-deficient recombinant adenovirus (Ad) encoding human gp100 or MART-1 melanoma Ag was used to transduce human dendritic cells (DC) ex vivo as a model system for cancer vaccine therapy [26].
• Clone DMF5, from a TIL infusion that mediated tumor regression clinically, showed the highest avidity against MART-1 expressing tumors in vitro, both endogenously in the TIL clone, and after RNA electroporation into donor T cells [27].
• To study the relationship between TCR affinity and cellular avidity, with the intent of identifying optimal TCR for gene therapy, we derived 24 MART-1:27-35 (MART-1) melanoma Ag-reactive tumor-infiltrating lymphocyte (TIL) clones from the tumors of five patients [27].

References